{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:08:28Z","timestamp":1772118508662,"version":"3.50.1"},"reference-count":53,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":2769,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2008,2]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:bold>Primary biliary cirrhosis (PBC) is an organ-specific autoimmune liver disease characterized by the presence of antimitochondrial antibodies and the destruction of small intrahepatic bile ducts with portal inflammation. In previous studies, we reported that both CD1d expression and the frequency of CD1d-restricted natural killer T (NKT) cells were increased in the livers of patients with PBC. To define a specific role of CD1d-restricted NKT cells in the pathogenesis of PBC, particularly early events, we investigated the function of hepatic CD1d-restricted NKT cells in our transforming growth factor \u03b2 (TGF-\u03b2) receptor II dominant-negative (dnTGF\u03b2RII) mouse model of PBC. We generated CD1d\u2212\/\u2212 and CD1d+\/\u2212 dnTGF\u03b2RII mice and performed a comparative study of liver immunopathology. We report herein that these dnTGF\u03b2RII mice demonstrate a massive increase of hyperactive CD1d-restricted NKT cells within the hepatic tissues. CD1d\u2212\/\u2212dnTGF\u03b2RII mice, which lack CD1d-restricted CD1d-restricted NKT cells, exhibit significantly decreased hepatic lymphoid cell infiltrates and milder cholangitis compared with CD1d+\/\u2212dnTGF\u03b2RII mice. Interestingly, there was a significant increase in the production of interferon-\u03b3 in hepatic CD1d-restricted NKT cells activated by \u03b1-galactosylceramide in young but not older dnTGF\u03b2RII mice, suggesting an age-dependent role of CD1d-restricted NKT cells.<\/jats:bold>\n                      <jats:bold>Conclusion:<\/jats:bold>\n                      <jats:bold>These data demonstrate that CD1d-restricted NKT cells in dnTGF\u03b2RII mice are a critical factor in liver injury. (Hepatology 2008.)<\/jats:bold>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.22052","type":"journal-article","created":{"date-parts":[[2007,12,20]],"date-time":"2007-12-20T22:46:53Z","timestamp":1198190813000},"page":"571-580","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":91,"title":["Natural killer T cells exacerbate liver injury in a transforming growth factor \u03b2 receptor II dominant-negative mouse model of primary biliary 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